Background and Objective: Opioid-induced hyperalgesia is a state of nociceptive sensitization which is induced by repeated exposure to opioids. In addition, this response also affects cognitive functions. The aim of this study was to examine blockade of NMDA receptors in mice with opioid-induced hyperalgesia on anxiety-like behavior. Method: Male NMRI mice were used in which opioid-induced hyperalgesia was established with injections of morphine 20 mg/kg (i.p.) twice per day on days 1–3 and 40 mg/kg (i.p.) twice per day on day 4. On day 5 (one day after the last injection) anxiety-like behaviors was assessed using an elevated-plus maze. The number of entries (with all four paws) into open and closed arms, and the total time in the open and closed arms were recorded. The percentage of open arm time (%OAT) and open arm entries (%OAE) used as the standard anxiety indices. Total closed arm entries were also recorded for each rat as an index for motor activity of the animal. Result: The results showed that MgSO4 at doses of 60, 120 and 240 mg/kg (i.p.) by itself did not significantly alter anxiety-like behaviors in normal mice but it induced anxiolytic-like behaviors in mice with history of opioid-induced hyperalgesia. The results also showed that MgSO4 at dose of 120 mg/kg (i.p.) along with morphine 10 mg/kg (i.p.) induced anxiogenic-like behaviors in mice with no history of opioid-induced hyperalgesia. Conclusions: In can be concluded that morphine-induced hyperalgesia affects anxiety-like behaviors at least partly via NMDA receptor system.
